Selective IgG deficiency with a transcriptional disorder of the gamma switching region gene and the IL-4 gene.
A primary immunodeficiency patient was analysed whose serum IgG and IgE were extremely low but whose IgM and IgA levels were within the normal range or elevated. Southern blot analysis indicated no deletion of structural genes coding for C gamma, C epsilon, or C alpha. The majority of the patient's peripheral B cells expressed IgM and IgD on the surface yet IgG-positive B cells were not detected, suggesting that the defect is in a switch-recombination process from IgM to IgG. The RFLP pattern detected with the S mu and S gamma DNA regions revealed that there was no deletion or large mutation in the switch region DNA. An in vitro IgG production system with pokeweed mitogen showed an abnormality at the transcriptional level and the defects were in both the patient's T and B cells. Addition of recombinant IL-4 (rIL-4) to the normal B cells enhanced IgG production but the patient's B cells did not respond to rIL-4, although the IL-4 receptor was present at the normal level. Messenger RNA and IL-4 protein were not produced in the patient's T cells upon stimulation with phorbol ester and calcium ionophore, whereas IL-2 was normally produced. The patient's lymphocytes showed a proliferative response to various mitogens, including phorbol ester. The transcripts of unrearranged C gamma region genes were not detected in the patient's lymphocytes, suggesting that the chromatin structure of the S gamma region may not be open. These results suggest that the transcriptional defects at the S gamma region gene in B cells and at the IL-4 gene in the T cells may be responsible for the present IgG immunodeficiency. There might be a common transcriptional system operating in a certain step in the activation of both genes.
Kaneko
H
H
Department of Pediatrics, Gifu University School of Medicine, Japan.
Nakashima
M
M
Kudo
A
A
Iwakiri
R
R
Harada
M
M
Watanabe
T
T
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D004406:Dysgammaglobulinemia / Q000235:genetics*; D005803:Genes, Immunoglobulin; D005812:Genes, Switch; D006801:Humans; D017099:IgG Deficiency; D007074:Immunoglobulin G / Q000235:genetics; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic
D007074:Immunoglobulin G; D015847:Interleukin-4